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Sökning: WFRF:(Fellman V)

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  • Purhonen, J., et al. (författare)
  • A spontaneous mitonuclear epistasis converging on Rieske Fe-S protein exacerbates complex III deficiency in mice
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We previously observed an unexpected fivefold (35 vs. 200 days) difference in the survival of respiratory chain complex III (CIII) deficient Bcs1/(p.S78G) mice between two congenic backgrounds. Here, we identify a spontaneous homoplasmic mtDNA variant (m.G14904A, mt-Cyb(p.D254N)), affecting the CIII subunit cytochrome b (MT-CYB), in the background with short survival. We utilize maternal inheritance of mtDNA to confirm this as the causative variant and show that it further decreases the low CIII activity in Bcs1/(p.S78G) tissues to below survival threshold by 35 days of age. Molecular dynamics simulations predict D254N to restrict the flexibility of MT-CYB ef loop, potentially affecting RISP dynamics. In Rhodobacter cytochrome bc(1) complex the equivalent substitution causes a kinetics defect with longer occupancy of RISP head domain towards the quinol oxidation site. These findings represent a unique case of spontaneous mitonuclear epistasis and highlight the role of mtDNA variation as modifier of mitochondrial disease phenotypes.
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  • Ahola, T, et al. (författare)
  • N-acetylcysteine does not prevent bronchopulmonary dysplasia in immature infants: A randomized controlled trial
  • 2003
  • Ingår i: Journal of Pediatrics. - 1097-6833 .- 0022-3476. ; 143:6, s. 713-719
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To evaluate whether N-acetyleysteine (NAC) infusion during the first week of life reduces the risk of death or bronchopulmonary dysplasia (BPD in infants with extremely low birth weight. Study design In a Nordic multicenter, double-blind trial, infants (n = 391) weighing 500 to 999 g and on ventilator or nasal continuous positive airway pressure were randomized before the age of 36 hours to receive NAC 16 to 32 mg/kg/d (n = 194) or placebo (n = 197) intravenously for 6 days. Primary end points were death or BPD, defined as supplementary oxygen requirement at 36 weeks' gestational age. Results There was no difference in the combined incidence of the primary end points death or BPD, 51% vs. 49%, between the NAC group and control group. Also similar was the incidence of BPD in survivors at 36 weeks' gestational age, 40% vs. 40%, and the mean oxygen requirement at the age of 28 days, 31.2% vs. 30.7%, respectively. The severity of BPD was similar in both groups. Conclusions A 6-day course of intravenous N-acetylcysteine at the dosage used does not prevent BPD or death in infants with extremely low birth weight.
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